title: Expeditious synthesis, enantiomeric resolution, and enantiomer functional characterization of (4-(4-bromophenyl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline-8-sulfonamide (4BP-TQS): an allosteric agonist-positive allosteric modulator of α7 nicotinic acetylcholine receptors.
abstract: An expeditious microwave-assisted synthesis of 4BP-TQS, its enantiomeric separation, and their functional evaluation is reported. Electrophysiological characterization in Xenopus oocytes revealed that activity exclusively resided in the (+)-enantiomer 1b (GAT107) and (-)-enantiomer 1a did not affect its activity when coapplied. X-ray crystallography studies revealed the absolute stereochemistry of 1b to be 3aR,4S,9bS. 1b represents the most potent ago-PAM of α7 nAChRs available to date and is considered for further in vivo evaluation.
authors.affiliation: Department of Pharmaceutical Sciences, Bouvé College of Pharmacy, Northeastern University , 140 The Fenway, 360 Huntington Avenue, Boston, Massachusetts, 02115, United States.
authors.forename: Ganesh A
authors.initials: GA
authors.lastname: Thakur
authors.forename: Abhijit R
authors.initials: AR
authors.lastname: Kulkarni
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Deschamps
authors.forename: Roger L
authors.initials: RL
authors.lastname: Papke
mesh_terms: D000494:Allosteric Regulation / Q000187:drug effects; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D008872:Microwaves; D008958:Models, Molecular; D015394:Molecular Structure; D009865:Oocytes / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014981:Xenopus; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000819:agonists*
chemical_list: C578201:4-(4-bromophenyl)-3a,4,5,9b-tetrahydro-3H-cyclopenta(c)quinoline-8-sulfonamide; D011804:Quinolines; D013449:Sulfonamides; D064569:alpha7 Nicotinic Acetylcholine Receptor